Voltage gated calcium channels, also known as voltage dependent calcium channels (VDCCs) are multisubunit membrane spanning proteins which permit controlled calcium influx from an extracellular environment into the interior of a cell. Several types of voltage gated calcium channel have been described in different tissues, including N-type, P/Q-type, L-type and T-type channels. A voltage gated calcium channel permits entry into the cell of calcium upon depolarization of the membrane of the cell, which is a lessening of the difference in electrical potential between the outside and the inside of the cell.
A voltage gated calcium channel contains several proteins, including α1, α2, β, and γ subunits. Subtypes of the calcium channel subunits also are known. For instance, α1 subtypes include α1A, α1B, α1C, α1D, α1E and α1S. Each subunit may have one or more isoforms which result from alternative splicing of RNA in the formation of a completed messenger RNA which encodes the subunit. For example, at least four isoforms of the rat N-type α1B subunit are known (see, e.g., Lin et al., Neuron 18:153-166, 1997).
Isoforms of calcium channel α1 subunits may be expressed differently in different tissues (see, e.g., Lin et al., 1997). Differential expression of subunits isoforms raises the possibility of developing therapeutics which are specific for distinct isoforms of the α1 subunits, thereby lessening side effects resulting from the use of therapeutics which are effective for more than one calcium channel isoform. Two isoforms of the human N-type calcium channel α1B subunit were published by Williams et al in 1992 (Science 257:389-395). Given the existence of several additional rat isoforms in a highly conserved gene family, it is surprising that additional human isoforms of the N-type calcium channel α1B subunit have not been discovered. Such isoforms would be useful for developing isoform-specific therapeutics.